Vial rubber-stopper

ABSTRACT

There is provided a rubber stopper used to seal an opened portion of vials and syringes for keeping medical liquid and, in particular, to a rubber stopper in which stoppering properties can be improved without damaging sealing properties in the absence of silicone coating. 
     A vial rubber stopper  1  comprises a disc-like top portion  3  and a cylindrical leg portion  2  of smaller diameter compared with that of the disc-like top portion, which is protruded from a bottom surface of the disc-like top portion  3  to shape into a flange  2 A upward. An under-flange ring portion  3 A connected to a flange bottom surface  2 B is divided on an outer peripheral surface of the cylindrical leg portion  2 , and the first ring-like raised portion  3 B and the second ring-like raised portion  3 C are formed downward of the under-flange ring portion  3 A in the circumferential direction. An upper surface of the disc-like top portion  3  including a flange-upper surface, a maximum diametral portion of a flange-peripheral surface, a bottom surface of the disc-like top portion  3  located inside of the cylindrical leg portion  2  and a surface of the cylindrical leg portion  2  other than the under-flange ring portion  3 A are laminated with a synthetic resin to leave the flange bottom surface and the surface of the under-flange ring portion  3 A as a naked rubber stock.

TECHNICAL FIELD

This invention relates to a rubber stopper used to seal an openedportion of vials and syringes as medical vessels which will behereinafter simply referred to as vial and, in particular, to a rubberstopper in which stoppering properties can be improved without damagingsealing properties in the absence of silicone coating.

BACKGROUND OF THE INVENTION

It is required for a stopper body used to seal an opened portion ofchemical or medical liquid-containing vial to meet various qualityrequirements such as sealing properties, gas barrier properties,chemical resistance, needling resistance, low reactivity and the likeand, in general, a rubber stopper body of high elastic deformation isfrequently employed as a product sufficient to satisfy theserequirements, which will be hereinafter referred to as rubber stopper.

A syringe needle is often stuck through the rubber stopper from an uppersurface thereof to suck up a chemical or medical liquid in a vial. Whenthe liquid kept in the vial is a medicine, the rubber stopper shouldmeet the quality requirement of the transfusion rubber stopper testaccording to the Japanese Pharmacopoeia, XV edition and, in speciality,should pass the elution test under a condition of 121° C. for one hourusing a heat resistant high pressure steam sterilizer.

There have been conventionally used synthetic rubbers such as butylenerubber and isoprene rubber, thermoplastic styrene elastomers such asSEBS, thermoplastic elastomers mainly comprising polyisobutylene andpolybutadiene, and the like as a material for vial rubber stopper whichmeets the requirement as described above.

With regard to a general figure of the vial rubber stopper, acylindrical leg portion is protruded downward from a disc-like topportion to form a flange upward, a diameter of the leg portion beingsmaller than that of the disc. The cylindrical leg portion of the vialrubber stopper is driven into an opened portion of the vial so that abottom surface of the flange of the disc-like top portion is stuckfirmly to an end surface of the opened portion.

Further, there has been proposed a vial rubber stopper in which aring-like protrusion is formed on the periphery of the cylindrical legportion to be driven into the opened portion of the vial, an outerdiameter of the protrusion being a little larger than an inner diameterof the opened portion (see, for example, the patent reference. 1 to 2).

Conventional vial rubber stoppers tend to stick each other on aconveying line during the production process to cause troubles of theline due to sticky nature of their surface.

In order to prevent such troubles, a silicone resin oil has beenconventionally coated on the surface of the rubber stopper. Coating ofsilicone oil is now avoided because of a potential harmful effect tohuman body.

On the other hand, there has been known another type of vial rubberstopper in which the full surface of the cylindrical leg portion to bein contact with a medical liquid and the bottom surface of the disc-liketop portion are laminated by an inactive resin film such as, forexample, quite chemically resistant fluorine resin film to preventchange in quality of the medical liquid contained in the vial and, atthe same time, to avoid mutual sticking of the rubber stoppers andimprove sliding properties thereof (see, the patent references 3 to 5).

It has been also known to laminate throughout the cylindrical legportion or partially a portion other than a peripheral root thereofcontinuing to the flange bottom surface, i.e., a ring portion under theflange for sealing the vial opened portion (see, the patent reference. 6to 9).

However, the above mentioned rubber stopper in which all surface of thecylindrical leg portion and the bottom surface of the flange arelaminated arouses difficulties in sealing properties of the vial becauseboth of these surfaces in contact with the vial opened portion are alllaminated with a laminate film.

In the case of the rubber stopper in which lamination is applied on thesurface other than that of the peripheral root portion of thecylindrical leg (ring portion under the flange), the peripheral rootportion is left as a naked rubber stock, thereby improving sealingproperties of the vial, while the rubber stopper sometimes comes up tothe surface after it is driven into the vial opened portion due tostrong friction and repulsion of the naked rubber stock, thereby causingsuch problems that the stopper might be driven repeatedly plural timesor is hardly to drive completely.

Further, in the case of the rubber stopper in which only the cylindricalleg portion is thoroughly laminated, friction resistance of the rubberstock is decreased but leakage of the naked rubber stock is occurredaround the peripheral root portion (ring portion under the flange) to beconnected to the bottom surface of the disc-like top portion when theleg is joined monolithically to the disc, thereby causing defectivemolding frequently.

The reason why is considered that the cylindrical leg portion set in amold is caught in a flow of the rubber stock for forming the flange ofthe disc-like top portion to cause difference in position, so that therubber stock flows into the thus formed gap between the mold and thecylindrical leg portion.

On the basis of the reason as described above, a vial rubber stopper GPas shown in FIG. 5 has been conventionally developed and used widely. Awide belt-like ring protrusion R is formed on a cylindrical leg portionL to keep sealing properties of a vial opened portion, while an inactivefilm lamination is applied on surfaces of the ring protrusion R and aportion as a periphery of a disc-like top portion T other than a bottomsurface T2 of a flange T1 as shown in FIG. 5 by a dark mesh pattern.

The bottom surface T2 of the flange T1 of the rubber stopper GP is notlaminated to leave it as a naked rubber stock, while the upper ringprotrusion R of the cylindrical leg portion L is coated with silicone tolower the friction resistance when the cylindrical leg portion L isdriven into the vial opened portion as shown in FIG. 5 by a faint meshpattern.

However, various harmful effects caused by silicone oil used forsilicone coating have been pointed out and are tried to avoid suchdisadvantages which include, for example, a decrease in strengthobserved when the silicone oil comes in contact with a medical liquidkept in the vial to absorb the active ingredient or an infection tohuman body caused by injection of the medical liquid contaminated with apealed material of silicone oil itself as fine particles. It is nowstudied to avoid silicone coating to the ring protrusion R of the vialrubber stopper GP as shown in FIG. 5.

Patent Reference 1: Japanese Utility Model No. 1986-2233

Patent Reference 2: Japanese Patent No. 1989-176435

Patent Reference 3: Japanese Patent No. 1990-136139

Patent Reference 4: Japanese Patent No. 2002-209975

Patent Reference 5: Japanese Patent No. 1988-296756

Patent Reference 6: U.S. Pat. No. 6,165,402

Patent Reference 7: Japanese Patent No. 1982-53184

Patent Reference 8: Japanese Utility Model No. 1986-31441

Patent Reference 9: Japanese Utility Model No. 1989-17545

DISCLOSURE OF THE INVENTION

This invention has been completed to solve conventional problems asdescribed above and accordingly it is an object of the invention is toprovide a vial rubber stopper of high sealing properties, gas barrierproperties, chemical resistance and needling resistance as well as lowreactivity, having improved productivity in the pharmaceuticalmanufacturing process and mechanical conveying properties, which isprepared without silicone coating.

In order to achieve the above mentioned object, a vial rubber stoppercomprises a disc-like top portion and a cylindrical leg portion ofsmaller diameter compared with that of the disc-like top portion, whichis protruded from a bottom surface of the disc-like top portion to shapeinto a flange upward, characterized in that an under-flange ring portionconnected to a flange bottom surface is divided on an outer peripheralsurface of the cylindrical leg portion, and at least one ring-likeraised portion is arranged downward of the under-flange ring portion inthe circumferential direction, while an upper surface of the disc-liketop portion including a flange-upper surface, a maximum diametralportion of a flange-peripheral surface, a bottom surface of thedisc-like top portion located inside of the cylindrical leg portion anda surface of the cylindrical leg portion other than the under-flangering portion are laminated with a synthetic resin to leave the flangebottom surface and the surface of the under-flange ring portion as anaked rubber stock.

Further, the under-flange ring portion is preferably divided between theflange bottom surface and a top edge portion of a synthetic resin filmlaminated on the outer peripheral surface of the cylindrical legportion. A material of the synthetic resin film is preferably afluororesin or Ultra High Molecular Weight polyethylene.

It is also preferable for preparing the vial rubber stopper of theinvention to conduct press molding of the cylindrical leg portion andlamination of the synthetic resin film thereto simultaneously and tocarry out press molding of the disc-like top portion, lamination of thesynthetic resin film thereto and integration of the disc-like topportion to the cylindrical leg portion at the same time.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view an embodiment of the present vial rubberstopper drawn from a diagonal downward direction, in which a meshpattern shows laminated portions.

FIG. 2 is a perspective view of a modification of the vial rubberstopper shown in FIG. 1.

FIG. 3 is a side view of the vial rubber stopper shown in FIG. 2, whichis monolithically molded.

FIG. 4 is a sectional view of the vial rubber stopper shown in FIG. 2,which is driven into an opened portion.

FIG. 5 is a perspective view of a conventional vial rubber stopper drawnfrom a diagonal downward direction, in which a dark mesh pattern showslaminated portions and a faint mesh pattern shows a silicone-coatedportion.

EFFECTS OF THE INVENTION

According to preferred embodiments of the invention, at least onering-like raised portion of a slightly larger diameter than that of thevial rubber stopper is formed on the outer peripheral surface of thecylindrical leg portion, which surface is laminated with an inactivesynthetic resin film of low friction resistance such as fluororesins.The under-flange ring portion of the cylindrical leg portion is left asa naked rubber stock, which is connected to the bottom surface of theflange arranged around the cylindrical leg portion, distance from theflange bottom surface to the nearest ring-like raised portion is in therange of ⅓ to 5 times of overall height of the ring-like raised portion.

Because of such structure of the present vial rubber stopper, thering-like raised portion arranged nearest to the flange bottom surfaceis pushed against an inner peripheral surface of vial opened portion tocause a shrinkage in diameter when the cylindrical leg portion is driveninto the vial opened portion, so that the under-flange ring portion as anaked rubber stock never comes in contact with the inner peripheralsurface of the vial opened portion. As a result, improved sealingproperties and high stoppering properties can be secured by the presentvial rubber stopper without applying conventional silicone coating.

In addition, as almost all surface of the cylindrical leg portion islaminated with an inactive synthetic resin film, it is possible to avoidcontamination of extraneous fine particles such as those eluted from thenaked rubber into the medical liquid in the vial.

As the flange bottom surface and the under-flange ring portion of thecylindrical leg portion are left as a naked rubber stock, the bottomsurface in such a naked situation is firmly joined to the surface of thevial opened portion when the present vial rubber stopper is driven intothe vial end portion, thereby high sealing properties being secured.

Further, when force in the upward direction is added to pull out thevial rubber stopper from the open portion, force in the downwarddirection acts to pull it down in the opposite direction against theunder-flange ring portion, thereby the ring-like raised portion beingdeformed to push the naked rubber stock of the under-flange ring portionagainst the inner peripheral surface of the vial opened portion. As aresult, the under-flange ring portion as the naked rubber stock isallowed to come in contact with the inner peripheral surface of the vialopened portion, thereby more improved sealing properties being obtained.

With regard to the present vial rubber stopper, the upper and bottomsurfaces of the disc-like top portion other than the flange bottomsurface, the maximum diametral portion of the flange-peripheral surfaceand the surface of the cylindrical leg portion other than theunder-flange ring portion are laminated with an inactive synthetic resinfilm such as fluororesins, thereby mutual sticking of rubber stopperbeing avoided to improve mechanical conveying properties thereof.

MOST PREFERABLE EMBODIMENTS OF THE INVENTION

As shown in FIG. 1, a vial rubber stopper 1 as an embodiment of theinvention comprises a shape in which a cylindrical leg portion 3 iscoaxially protruded from a bottom surface of a thick top disk portion 2,a diameter thereof being smaller than that of the than that of thedisc-like top portion and a surrounding edge of the disc-like topportion 2 being overhung from upward of the cylindrical leg portion 3 toform a flange 2A.

An under-flange ring portion 3A is divided in a circular form ofpredetermined width on an upper end portion of the cylindrical legportion 3, which is connected to a bottom surface 2A1 of the flange 2A.First and second ring-like raised portions 3B and 3C are formed on aperipheral surface of the cylindrical leg portion 3 below theunder-flange ring portion 3A at a predetermined interval in the verticalaxial direction and extended in the circumferential direction parallelto the under-flange ring portion 3A.

With regard to a vial rubber stopper 1 shown in FIG. 2 as a modifiedexample of the embodiment of FIG. 1, there are formed a cutaway portion3E on the cylindrical leg portion 3 and a separate-type raised portion3D on the outer peripheral surface thereof.

The cutaway portion 3E is formed by cutting the cylindrical leg portion3 upwardly from a tip side opposed to the under-flange ring portion 3Ato a line between the first and the second ring-like raised portions 3Band 3C in the axial direction at a predetermined interval. The cutawayportion 3E is shown only one in FIG. 2 but may be formed plurally and,in the case of plurality, each one may be the same size and opposingeach other, or may be random size and arranged randomly.

The separate-type raised portion 3D is formed below the second ring-likeraised portion 3C parallel thereto and divided in the circumferentiallydirection, which cross-sectional shape is, for example, nearly triangleto keep stability.

Cross-sectional shape of the first ring-like raised portion 3B arrangedabove the cutaway portion 3E and the second ring-like raised portion 3Ccut off by the cutaway portion 3E may be semicircular, semi-oval,triangle, rectangular, trapezoid or any others. Those portions 3B and 3Cshown in FIG. 1 may also be shaped similarly.

With regard to the vial rubber stopper 1 shown in FIG. 2, the firstring-like raised portion 3B arranged above the cutaway portion 3E may benot only one but formed plurally.

It is preferable that a maximum outer diameter of the first and thesecond ring-like raised portions 3B and 3C shown in FIG. 1 and that ofsimilar portions 3B and 3C shown in FIG. 2 are slightly larger, and moredefinitely about 1% to 30% larger, than a caliber of a vial B openedportion shown in FIG. 4, i.e., diameter of an opened inner peripheralportion B1. An increase in maximum outer diameter as described abovemakes it possible to secure high sealing properties and stopperingproperties when the vial rubber stopper is driven into the vial B openedportion.

Such the increase in diameters of the first and the second ring-likeraised portions 3B and 3C varies depending on elasticity of a rubberstock to be used for the rubber stopper 1 and a material of the vial B(glass or synthetic resins) and is not necessarily fixed, although it isdesirable to increase diameters thereof in the range of about 1% to 30%compared with a caliber of the vial B when elasticity of a syntheticresin used as a material of the vial B is about 2 to 2.5 GPa and Shore Ahardness of a rubber stock used as the rubber stopper 1 is about 15 to45.

It is especially desirable to increase the maximum outer diameter of theuppermost first ring-like raised portion 3B which greatly influencessealing properties and stoppering properties of the rubber stopper 1 tothe vial B opened portion. Excessively smaller diameter causes poorsealing properties and stoppering properties, while in contrast, it isdifficult to drive the rubber stopper and seal the vial satisfactorilyif the diameter is too large.

The uppermost first ring-like raised portion 3B is preferably arrangedto be fallen in a length range from ⅓ to 5 times of overall heightthereof in the downward direction from an upper edge of the under-flangering portion 3A which coincides in arrangement with the bottom surface2A1 of the flange 2A. That is to say, the shortest interval of thenearest first ring-like raised portion 3B from the bottom surface 2A1 ofthe flange 2A is preferably fallen in the range from ⅓ to 5 times ofoverall height thereof.

If the uppermost first ring-like raised portion 3B is arranged on anexcessively low location, or if the shortest interval from the bottomsurface 2A1 of the flange 2A to the first ring-like raised portion 3B ismore than 5 times of overall height thereof, the rubber stock of theunder-flange ring portion 3A comes in contact with the inner peripheralsurface B1 of the vial B opened portion, thereby causing failure instoppering and loosing sealing properties of the vial B.

In contrast with this, if the uppermost first ring-like raised portion3B is arranged on an excessively high location, or if the shortestinterval from the bottom surface 2A1 of the flange 2A to the firstring-like raised portion 3B is less than ⅓ time of overall heightthereof, it is difficult to mold the rubber stopper 1, which makes themolding yield worse.

An optimum location of the first ring-like raised portion 3B variesdepending on hardness and size of the rubber stopper 1. Hardness (ShoreA) of a rubber stock within the optimum designed value is about 15 to 45and size of the rubber stopper 1 is about 5 to 50 mm in diameter.

With regard to the present vial rubber stopper 1, the bottom surface 2A1of the flange 2A is left as a naked rubber stock. Further, the bottomsurface 2A1 is molded to adhere to an edge surface B2 of the openedportion of the vial B shown in FIG. 4. When the vial B is made of asynthetic resin, the edge surface B2 of the opened portion is generallyshaped into flat and, accordingly, the bottom surface 2A1 of the flange2A is preferably flat.

With regard to the present vial rubber stopper 1, the upper surface ofthe disc-like top portion 2 including the upper surface of the flange2A, the maximum diametral portion 2A2 of the peripheral surface of theflange 2A, the bottom surface of the disc-like top portion 2 arranged inthe cylindrical leg portion 3 and the surface including the outer andinner peripheral surfaces of the cylindrical leg portions 3 other thanthe under-flange ring portion 3A are laminated with a synthetic resinfilm as shown in FIG. 1 or FIG. 2 (see, mesh patterns drawn therein). Onthe other hand, the bottom surface 2A1 of the flange 2A and the surfaceof the under-flange ring portion 3A of the cylindrical leg portion 3 areleft as a naked rubber stock.

An upper edge of the synthetic resin film laminated on the outerperipheral surface of the cylindrical leg portion 3 is fit upward overthe first ring-like raised portion 3B, which the nearest location to thebottom surface 2A1 of the flange 2A, so that the under-flange ringportion 3A is divided between the upper edge and the bottom face 2A1.

If vertical width of the under-flange ring portion 3A is excessivelynarrow, it is difficult to mold the vial rubber stopper 1, while toowide width thereof increases frictional resistance of the rubber stock,thereby decreasing stoppering properties of the vial rubber stopper 1.Accordingly, the upper edge of the synthetic resin film is preferablyfit downward of the bottom surface 2A1 of the flange 2A at an intervalof 0.5 mm or more so as to leave vertical width of 0.5 mm or more forthe under-flange ring portion 3A.

The cutaway portion 3E formed on the cylindrical leg portion 3 of thevial rubber stopper 1 shown in FIG. 2 is effective as will be describedin the following. For example, when a solvent or water component in amedical liquid charged in the vial B shown in FIG. 4, should be removed,the vial B with the medical liquid charged therein is placed in anappropriate device such as vacuum dryer while keeping the vial rubberstopper 1 in a half-driven situation. Then, the solvent or watercomponent contained in the vial B is evaporated and suctioned outthrough the cutaway portion 3E when the vacuum dryer is operated, themedical liquid being thus vacuum dried. Such a half-driven situation ofthe vial rubber stopper 1 can be kept satisfactorily by means of theseparate-type raised portion 3D which is separated in thecircumferential direction and has a triangle cross-section.

FIG. 3 is an illustration of vial rubber stopper 1 shown in FIGS. 1 and2 in which the rubber stopper 1 is placed in a mold in the course ofmolding. The cylindrical leg portion 3 is subjected to press molding tomonolithically mold (laminate) with a synthetic resin film (drawn asmesh patterns in FIG. 3), punched out and set in a bottom force (notshown).

A material of the disc-like top portion 2 is placed on the cylindricalleg portion 3 in the above mentioned situation, while a synthetic resinfilm is put on the stock which is then press-molded by means of a force(not shown). Accordingly, press molding of the disc-like top portion 2,lamination of the disc-like top portion 2 with the synthetic resin filmand unification of the disc-like top portion 2 and the cylindrical legportion 3 are conducted at the same time. The laminated disc-likeportion 2 is drawn by mesh patterns in FIG. 3 and implies a continuoussurface ranging from the upper surface of the disc-like top portion 2,which includes the upper surface of the flange 2A, and the maximumdiametral portion 2A2 of the peripheral surface of the flange 2A.

The synthetic resin film used to laminate the cylindrical leg portion 3and that of used to laminate the maximum diametral portion 2A2 of theperipheral surface of the flange 2A may be the same or different. Afluororesin film is preferably used either in the case of same ordifferent, and different fluororesin films are preferably selected inthe case of different. An Ultra High Molecular Weight polyethylene resinfilm is also used preferably as a synthetic resin film other than afluororesin form standpoints of thermal resistance, chemical resistance,etc.

As two rubber stocks come in contact with each other when thecylindrical leg portion 3 and the disc-like top portion 2 are unified asshown in FIGS. 1 to 3, each rubber stock does not exert any badinfluence upon their unification, if the same or different rubber stockuseful for unifying these two portions 2 and 3 is used even when thesynthetic resin film to be laminated is the same or different.

The rubber stock for comprising the disc-like top portion 2 and thecylindrical leg portion 3 of the present vial rubber stopper 1 is notrestricted to a specific one, if the material is tough and hasappropriate hardness, impact resilience and other excellent propertiessuch as thermal resistance, aging resistance, chemical resistance, gasbarrier properties, low eluting properties and low reactivity.

Rubber stocks used in the present invention include, for example, butylrubber, i.e., isoprene-isobutylene copolymer, halogenated butyl rubberprepared by chlorinating or brominating butyl rubber,acrylonitrile-butadiene copolymer rubber, isoprene terpolymer, isoprenerubber, butadiene rubber, styrene-butadiene rubber, ethylene-propylenerubber, ethylene-propylene-diene rubber, chloro-sulfonated polystyrene,ethylene-vinyl acetate copolymer, styrene-ethylene-butylene-styrene(SEBS) thermoplastic elastomer, thermoplastic elastomer comprisingpolyisobutylene and polybutadiene as a main component, and a rubberstock in which synthetic rubber such as styrene-isoprene rubber ornatural rubber is used as a main component and added with filling agent,cross-linking agent, etc. to secure physical properties and thermalresistance sufficient to a rubber stopper.

Above all, butyl rubber, halogenated butyl rubber, and thermoplasticelastomer comprising polyisobutylene or polybutadiene as a maincomponent are preferable rubber stocks not only for a reason that theymeet the requirements as described above but from a standpoint of theirhigh gas-impermeability, ozone resistance, aging resistance and adhesiveproperties.

A fluororesin film is preferably used as a synthetic resin film forlaminating the present vial rubber stopper 1, which can be laminated onthe rubber stock as an inactive synthetic resin film and has highthermal resistance and chemical resistance as well as lower frictionalresistance compared with that of the rubber stock. The fluororesinincludes, for example, tetrafluoroethylene resin (PTFE),tetrafluoroethylen-perfluoroethylene copolymer (PFA),tetrafluoroethylene-hexafluoroethylene copolymer (FEP),tetrafluoroethylene-ethylene copolymer (ATFE),trichlorotrifluoroethylene (PCTFE), polyfluorinated vinylidene (PVDF),polyfluorinated vinyl (PVF), etc.

Tetrafluoroethylene resin, which will be hereinafter referred to asPTFE, is especially preferable by the following reasons. PTFE isconsiderably stable so that it does not solve or swell almost allchemicals, and is one of the most thermally resistant organic materials,simply results in transparent gel but does not exhibit melt-flowcharacteristics when it is melted at the melting point of 327° C. andhas so high continuous working temperature as about 260° C., while itssurface is extremely hydrophobic, oil-repellent and non-adhesive andexhibits low frictional resistance and high sliding properties. Becauseof intrinsic advantages as described above, PTFE is sufficientlyresistant to high temperature sterilizing treatments in the course ofpharmaceutical and other processes. Furthermore, when PTFE laminated onthe vial rubber stopper 1 comes in contact with chemicals charged in thevial for a long period of time, the laminated material does not absorbthe chemicals and nothing is eluted from the lamination, thereby provingchemical stability thereof. PTFE is sufficiently slidable to pressinglydrive the rubber stopper into the vial after charging chemicals therein,so that it possesses characteristics to meet physical and chemicalproperties to be expected as a surface laminating film material, whichis used to laminate sealing stoppers for sealing vial containers.

An Ultra High Molecular Weight polyethylene resin film may also bepreferably used as a laminating material other than the fluororesin filmfrom a standpoint of thermal resistance, chemical resistance, etc. TheUltra High Molecular Weight polyethylene refers to those polyethylenepolymers of about 100 million to 700 million in molecular weight.

Thickness of the inactive synthetic resin film such as the abovementioned fluororesin film is preferably about 0.001 to 0.3 mm, morepreferably 0.01 to 0.2 mm and most preferably 0.02 to 0.15 mm, and thethickness fallen in this range lowers voids of thin film, therebyreducing the defectiveness level of products with advantage. Anexcessively thinner film makes it difficult to yield the products andwould cause processing failure and inadequate certification of products,while excessively thicker one raises rigidity of the film extremely sothat sealing properties and needling resistance of a completed rubberstopper deteriorate inadequately.

In order to secure a rigid adhesion surface between an inactivesynthetic resin film such as a fluororesin film as described above and arubber stock surface, a surface of the synthetic resin film ispreferably cleaned or treated by means of, primer treatment, coronadischarge, plasma discharge, glow discharge, arc discharge, sputteredetching and the like, thereby adhesion between the film and the rubberstock being strengthened.

The preferred adhesive strength is about 1 to 30 kg/cm. When theadhesive strength is excessively low, exfoliation of the film from therubber stock possibly occurs not only in the course of pharmaceuticalprocessing but during a storage period after pharmaceutical preparationor under an as-used condition such as needling, and on the contrary,excessively high adhesive strength is no more than saturation ofadhesive effect and is not economical.

As has been described above referring to FIG. 3, the present vial rubberstopper 1 is molded in the following manner. The cylindrical leg portion3, which has been laminated by press molding in advance, is set in thebottom force (not shown). A molding stock of the disc-like top portion 2and a laminating synthetic resin film are placed on the upper surface ofthe leg portion 3, followed by press molding of the synthetic resin filmand the molding stock by means of a force (not shown). Molding of thedisc-like top portion 2, lamination of the synthetic resin film on theleg portion 2 and unification of the cylindrical leg portion 3 areconducted simultaneously.

More in detail, the laminating synthetic resin film is placed on thebottom force (not shown) for molding the cylindrical leg portion 3 firstof all, on which an uncured rubber stock to be used to mold thecylindrical leg portion 3 is placed. The cylindrical leg portion 3 ismolded and cured by means of press molding and, at the same time, acontinuous surface covering over the inner peripheral surface of thecylindrical leg portion 3 and the outer peripheral surface thereof islaminated, the outer peripheral surface including the first ring-likeraised portion 3B, the second ring-like raised portion 3C and theseparate-type raised portion 3D. Then, the bottom force is opened totake out the cylindrical leg portion 3 which is laminated by thesynthetic resin film and cut into a predetermined shape.

After that, the thus laminated and cut cylindrical leg portion 3 iscleaned and set in a bottom force (not shown), while the uncured rubberstock to be used for molding the disc-like top portion 2 is placedthereon, and then the laminating synthetic resin film is put on theupper surface of the rubber stock, followed by clamping by means of aforce (not shown) and press-molding under pressure of about 50 to 150kg/cm² at temperature ob about 150 to 200° C.

In this way, curing and molding of the disc-like top portion 2,lamination of a continuous surface covering from the upper surface ofthe disc-like top portion 2 to the maximum diametral portion 2A2 of theperipheral surface of the flange 2A, and unification of the disc-liketop portion 2 and laminated cylindrical leg portion 3 are conducted atthe same time. The force (not shown) is opened to take out the product,which is then cut from the middle of the peripheral surface of theflange 2A in the diagonal inside direction as shown in FIG. 3 by a line“x” and washed to yield the present vial rubber stopper 1.

According to the above mentioned embodiment, molding of the disc-liketop portion 2 and lamination thereof are conducted by means of themolding tool for molding the disc-like top portion 2, but there may beused the bottom force for molding the cylindrical leg portion 3 inanother embodiment.

Further, each rubber stock to be used for molding the cylindrical legportion 3 and the disc-like top portion 2 may either be the samecomposition or different one as described above, if each rubber stockcan be unified.

An applied example of the present vial rubber stopper 1 is shown in FIG.4. After a medical liquid M is charged in the vial B, the cylindricalleg portion 3 of the present vial rubber stopper 1 is inserted anddriven into the opened portion of the vial B along the inner peripheralsurface B1 to adhere the bottom surface 2A1 of flange 2A of thedisc-like top portion 2 to the edge surface B2 of the opened portion.The disc-like top portion 2 is covered with an aluminum cap A to caulkaround the opened portion of the vial B and seal it. Complete seal ofthe vial B is thus secured.

Example

A plate stock of uncured rubber composition shown in Table 1 was used asa rubber stock for molding the cylindrical leg portion 3 and thedisc-like top portion 2. There was used “Dai D3” (0.05 mm in thickness),available from Nitto Denka Corporation, as an inactive synthetic resin(PTFE) for laminating the cylindrical leg portion 3 and the disc-liketop portion 2.

TABLE 1 Composition of Rubber Stock Parts by Weight butyl rubber 100 wetwater-containing silica ⁽¹⁾ 30 zinc oxide ⁽²⁾ 1.51,1-bis(t-butylperoxide)-3,3,5-trimethylhexane ⁽³⁾ 2 ⁽¹⁾ Nipushiiru ER;available from Nippon Sirika Kogyo ⁽²⁾ Active Chinese White AZO;available from Seido Kagaku Kogyo ⁽³⁾ Perhexane 3M-40; available fromNOF Corporation

As shown in FIG. 3, using a bottom force (not shown), press molding andlamination of the cylindrical leg portion 3 was conducted at the sametime under a condition of molding pressure: 100 kg/cm² and moldingtemperature: 165° C., followed by opening and releasing of the force andwashing.

There used two kinds of bottom forces as detailed in the following:

(1) A bottom force provided with concaves for forming the first and thesecond ring-like raised portions 3B and 3C having overall height shownin Table 2 and of semicircular in cross section; and

(2) A bottom force provided with, in addition to these concaves for thefirst and the second ring-like raised portions 3B and 3C, concaves forforming separate-type raised portion 3C having overall height shown inTable 2 and of nearly triangle in cross section.

With regard to these two kinds of bottom forces, maximum outer diameters(maximum height of the raised portions) of the first and the secondring-like raised portions 3B and 3C as well as the separate-type raisedportion 3D are sums of doubled dimensions of their overall height shownin Table 2 and diameter of the cylindrical leg portion 3 as shown inTable 2, respectively.

Vertical width of the under-flange ring portion 3A divided on the upperend portion of the cylindrical leg portion 3 are also shown in Table 2.

TABLE 2 dimension of vial rubber stopper 1 (mm) 10 ml-vial 20 ml-vialdiameter of flange 2A 19 13 diameter of 14 7.5 cylindrical leg portion 3Length of 10 7 cylindrical leg portion 3 vertical width of 1 0.6 underflange ring portion 3A overall height of 0.3 0.3 first ring-like raisedportion 3B overall height of 0.3 0.3 second ring-like raised portion 3Coverall height of 0.3 0.3 separate type raised portion 3D caliber ofopened 13 7 portion of vial B

After the cylindrical leg portion 3 was washed and set in the bottomforce (not shown), the plate stock of uncured rubber composition shownin Table 1 and the laminating synthetic resin film were placed thereonand then press molding of the disc-like top portion 2, lamination of thesynthetic resin and unification of the disc-like top portion 2 and thecylindrical leg portion 3 were conducted at the same time under the samepressure and temperature condition as described above, followed byopening of the bottom force, cutting as shown in FIG. 3 by the line “x”and washing.

The thus yielded vial rubber stopper 1 was driven into the openedportion of commercial vials B and it was found that every tested rubberstopper 1 was fitted therein satisfactorily. The vials B were chargedwith water and kept in a half-stoppered situation with the rubberstopper 1, followed by drying in a vacuum dryer under pressure of 0.5kg/cm² and at temperature of 25° C. for 24 hours. As a result, 90% ofwater was removed from all of the vials B sealed with the rubber stopper1 on which the separate-type raised portion 3D is formed and, on theother hand, a breakdown of such the half-stoppered situation wasobserved in the course of drying in many cases of the rubber stopper 1on which the raised portion 3D is not formed and, what is worse, onlyless than 50% of water was removed in some cases or complete stopperingwas not sustained after 24 hour drying in other cases.

Comparative Example

A conventional vial rubber stopper GP shown in FIG. 5 was used to repeata stoppering test and a vacuum drying test in a similar manner asdescribed above. As a result, it was found that a stoppering process wasperformed unsatisfactorily in the stoppering test because ofconsiderable frictional resistance caused by rubber stock used as a widebelt ring-like raised portion R, while in the vacuum drying test, vacuumdrying itself was performed favorably but the stoppering process aftervacuum drying was not proceeded successfully.

INDUSTRIAL APPLICABILITY

The present vial rubber stopper is conveniently applicable to variousvials provided with an opened portion of different calibers. Further,the present stopper can be applied not only to embodiments in which aninjection needle pierces the top portion but to those cases in which noneedle pierces the top portion.

1. A vial rubber stopper comprises a disc-like top portion and acylindrical leg portion of smaller diameter compared with that of thedisc-like top portion, which is protruded from a bottom surface of thedisc-like top portion to shape into a flange upward, characterized inthat an under-flange ring portion connected to a flange bottom surfaceis divided on an outer peripheral surface of the cylindrical legportion, and at least one ring-like raised portion is arranged downwardof the under-flange ring portion in the circumferential direction, whilean upper surface of the disc-like top portion including a flange-uppersurface, a maximum diametral portion of a flange-peripheral surface, abottom surface of the disc-like top portion located inside of thecylindrical leg portion and a surface of the cylindrical leg portionother than the under-flange ring portion are laminated with a syntheticresin to leave the flange bottom surface and the surface of theunder-flange ring portion as a naked rubber stock.
 2. A vial rubberstopper claimed in claim 1 in which shortest interval from a bottomsurface of said flange to a ring-like raised portion nearest thereto isfallen in a range from ⅓ to 5 times of the ring-like raised portion. 3.A vial rubber stopper claimed in claim 1 in which maximum diameter of aring-like raised portion nearest to a bottom surface of said flange is 1to 30% larger than a caliber of an opened portion of a vial to beinserted thereto said cylindrical leg portion.
 4. A vial rubber stopperclaimed in claim 1 in which said under-flange ring portion is dividedbetween a bottom surface of said flange and an upper edge portion of asynthetic resin film to be laminated on an outer peripheral surface ofsaid cylindrical leg portion.
 5. A vial rubber stopper claimed in claim1 in which a material of said synthetic resin film is either afluororesin or Ultra High Molecular Weight polyethylene.
 6. A vialrubber stopper claimed in claim 1 in which press molding of saidcylindrical leg portion and lamination of a synthetic resin film ontosaid cylindrical leg portion are conducted at the same time, while pressmolding of said disc-like top portion, lamination of a synthetic resinfilm onto said disc-like top portion and unification of said disc-liketop portion and said cylindrical leg portion are conducted at the sametime.